Ca2+ Selective Host Rotaxane Is Highly Toxic Against Prostate Cancer Cells.
ABSTRACT: New therapies are needed to eradicate androgen resistant, prostate cancer. Prostate cancer usually metastasizes to bone where the concentration of calcium is high, making Ca2+ a promising toxin. Ionophores can deliver metal cations into cells, but are currently too toxic for human use. We synthesized a new rotaxane (CEHR2) that contains a benzyl 15-crown-5 ether as a blocking group to efficiently bind Ca2+. CEHR2 transfers Ca2+ from an aqueous solution into CHCl3 to greater extent than alkali metal cations and Mg2+. It also transfers Ca2+ to a greater extent than CEHR1, which is a rotaxane with an 18-crown-6 ether as a blocking group. CEHR2 was more toxic against the prostate cancer cell lines PC-3, 22Rv1, and C4-2 than CEHR1. This project demonstrates that crown ether rotaxanes can be designed to bind a targeted metal cation, and this selective cation association can result in enhanced toxicity.
Project description:In this article, a six-component self-sorting process that involves three types of crown ether macrocycle and three types of cation guest molecule was carefully and thoroughly investigated. The six components include three kinds of crown ether, namely bis(p-phenylene-34-crown-10) (BPP34C10), dibenzo-24-crown-8 (DB24C8) and benzo-21-crown-7 (B21C7), and their corresponding cation guest molecules, namely a 4,4'-bipyridine dication (BPY2+) and dibenzylammonium (DBA) and benzylalkylammonium (BAA) ions, respectively. Based on this well-established highly selective six-component self-sorting process, a heterorotaxane bearing three different kinds of crown ether macrocycle was designed and successfully synthesized through a facile and efficient one-pot "click" stoppering strategy. Such work is proposed to be a significant advance in the construction of mechanically interlocked molecules with high structural complexity, as well as a good supplement in the areas of multi-component self-sorting and noncovalent self-assembly.
Project description:Noncovalent interactions of organic moieties with Lewis acidic alkali cations can greatly affect structure and reactivity. Herein, we describe the effects of interactions with alkali-metal cations within a series of reduced iron complexes bearing a redox-active formazanate ligand, in terms of structures, magnetism, spectroscopy, and reaction rates. In the absence of a crown ether to sequester the alkali cation, dimeric complexes are isolated wherein the formazanate has rearranged to form a five-membered metallacycle. The dissociation of these dimers is dependent on the binding mode and size of the alkali cation. In the dimers, the formazanate ligands are radical dianions, as shown by X-ray absorption spectroscopy, Mössbauer spectroscopy, and analysis of metrical parameters. These experimental measures are complemented by density functional theory calculations that show the spin density on the bridging ligands.
Project description:The reaction of dimethyl-amine, 18-crown-6, and perchloric acid in methanol yields the title compound, C(2)H(8)N(+)·ClO(4) (-)·C(12)H(24)O(6)·H(2)O. The dimethyl-ammonium cation and the water mol-ecule inter-act with the 18-crown-6 unit: N-H?O hydrogen bonds are formed between the ammonium NH(2) (+) group and four O atoms of the crown ether, while the water mol-ecule on the other side of 18-crown-6 ring forms O-H?O hydrogen bonds with two other O atoms of the crown ether. All conventional donors and acceptors in the cations are thus engaged in hydrogen bonding. The ClO(4) (-) anion is disordered over two sites, and occupancies for the disordered O atoms were fixed at 0.5. In the crystal, the cations and anions are arranged in alternating layers.
Project description:In the title compound, 2CH(6)N(3) (+)·2Br(-)·C(12)H(24)O(6), the 18-crown-6 mol-ecule lies about an inversion center, whereas the guanidinium cation and bromide anion are in general positions. The guanidinium cations link with the bromide anions and the crown ether mol-ecules via N-H?O and N-H?Br hydrogen bonds, thus forming a three-dimensional network.
Project description:We report a one-step enantioselective synthesis of mechanically planar chiral rotaxanes. Previous studies of such molecules have generally involved the separation of enantiomers from racemic mixtures or the preparation and separation of diastereomeric intermediates followed by post-assembly modification to remove other sources of chirality. Here, we demonstrate a simple asymmetric metal-free active template rotaxane synthesis using a primary amine, an activated ester with a chiral leaving group, and an achiral crown ether lacking rotational symmetry. Mechanically planar chiral rotaxanes are obtained directly in up to 50% enantiomeric excess. The rotaxanes were characterized by NMR spectroscopy, high-resolution mass spectrometry, chiral HPLC, single crystal X-ray diffraction, and circular dichroism. Either rotaxane enantiomer could be prepared selectively by incorporating pseudoenantiomeric cinchona alkaloids into the chiral leaving group.
Project description:Switchable crown ether-ammonium rotaxanes with a redox-active tetrathiafulvalene (TTF) unit implemented in their wheels were synthesised and fully characterised. Reversible operation in two modes is possible, in which the rotaxane's axle is either charged or neutral. Cyclic voltammetry experiments reveal the effects of mechanical bonding on the electrochemical properties of TTF and show the rotaxanes to perform a distinct function in both modes. In the charged mode, redox-switching is dominated by strong electrostatic repulsion in the rotaxane which subsequently leads to a macrocycle translation along the axle. In the non-charged mode, a selective energetic stabilisation of TTF radical cations is observed, which can be attributed to an interplay of weak electrostatic interactions between wheel and axle.
Project description:In the crystal structure of the title compound, NH(4) (+)·PF(6) (-)·C(12)H(24)O(6), the cation is situated in the 18-crown-6 ring, forming a supra-molecular rotator-stator-like structure held by N-H?O hydrogen bonds. The six O atoms of the crown ether lie approximately in a plane [mean deviation 0.2129?(3)?Å]; the N atom is displaced by 0.864?(3)Å from the centroid of the 18-crown-6 ring. The slightly distorted tetra-hedral cations further inter-act with the slightly distorted octa-hedral anions via inter-molecular N-H?F hydrogen bonds.
Project description:We report on a rotaxane-like architecture secured by the in?situ tying of an overhand knot in the tris(2,6-pyridyldicarboxamide) region of the axle through complexation with a lanthanide ion (Lu3+ ). The increase in steric bulk caused by the knotting locks a crown ether onto the thread. Removal of the lutetium ion unties the knot, and when the axle binding site for the ring is deactivated, the macrocycle spontaneously dethreads. When the binding interaction is switched on again, the crown ether rethreads over the 10?nm length of the untangled strand. The overhand knot can be retied, relocking the threaded structure, by once again adding lutetium ions.
Project description:A tetrathiafulvalene (TTF)-containing crown ether macrocycle with C s symmetry was designed to implement planar chirality into a redox-active rotaxane. The directionality of the macrocycle atom sequence together with the non-symmetric axle renders the corresponding rotaxane mechanically planar chiral. Enantiomeric separation of the rotaxane was achieved by chiral HPLC. The electrochemical properties - caused by the reversible oxidation of the TTF - are similar to a non-chiral control. Reversible inversion of the main band in the ECD spectra for the individual enantiomers was observed after oxidation. Experimental evidence, conformational analysis and DFT calculations of the neutral and doubly oxidised species indicate that mainly electronic effects of the oxidation are responsible for the chiroptical switching. This is the first electrochemically switchable rotaxane with a reversible inversion of the main ECD band.
Project description:In the title compound, C(7)H(10)N(+)·BF(4) (-)·C(12)H(24)O(6), the proton-ated 4-methyl-anilinium cation inter-acts with 18-crown-6 forming a rotator-stator structure, (C(6)H(4)CH(3)NH(3) (+))(18-crown-6), through three bifurcated N-H?(O,O) hydrogen bonds between the ammonium groups of the cations (-NH(3)) and the O atoms of the crown ether mol-ecule. The BF(4) (-) anions, the methyl group and the protonated -NH(3) groups of the 4-methylanilinium lie on a dual axis of rotation. The 18-crown-6 unit is perpendicular to the dual axis of rotation and the mirror plane which contains the dual axis of rotation. The benzene ring of 4-methylanilinium is perpendicular to the mirror plane and parallel to the dual axis.